Cell death and a-beta levels

Professor Dennis Selkoe discusses the largely linear relationship between a-beta and cell death in the brain.

There is a linear relationship between a-beta build-up and neuronal dysfunction, and ultimately neuronal death. Nowadays in Alzheimer’s disease we are more interested in the subtle dysfunction of a neuron, long before it gives up the ghost. So we don’t even talk or focus as much on neuronal death, although unequivocally that happens in the fullness of time with Alzheimer’s [disease] patients. By and large there is a linear relationship. It’s not a perfect line; it’s scattered along an axis that goes up diagonally between a-beta amount and age, but within that scatter you can draw a statistically significant relationship. So that happens, for example, and we’ve published some of this work some years ago. It happens with a-beta levels and ApoE4. There is a correlation between ApoE4 genotype and a linear rise in a-beta buildup. The more a-beta you get, you eventually exceed a threshold, and then you’re very likely to have enough a-beta in your brain that these doublets and triplets and quadruplets and perhaps somewhat higher oligomers are going to short circuit nerve cells in the hippocampus and cause synaptic function to decline. So, by and large, it’s a quantitative issue, not a qualitative issue in Alzheimer’s [disease], at least that’s what we believe right now.